Disuse osteoporosis increases fracture risk for patients who have had a stroke or spinal cord injury. Animals also lose bone mass and strength during inactivity because bone formation is uncoupled from resorption. Cortical bone mineral apposition rate is reduced approximately 50% in hind-limb suspended rats compared to controls. During disuse, intracortical porosity increases and bone strength decreases. In humans, bone loss during disuse is associated with increased calcium excretion. In contrast, bears do not eat, drink, urinate, or defecate (i.e., excrete calcium) during hibernation, and blood calcium concentration remains constant throughout the year. There is some evidence to suggest that bone formation remains coupled to bone resorption in hibernating bears. Thus, bone mass and strength losses should be small, if they occur at all, in bears during hibernation (i.e., disuse). In this research proposal, it is hypothesized that bears maintain bone cross-sectional properties and strength during annual periods of disuse because they maintain bone formation. If this is true, it will support the idea that bears have biological mechanisms to prevent disuse osteoporosis. Elucidating the biological mechanisms may help us design therapies to treat human osteoporoses. This may be accomplished by targeting genes and circulating hormones which are differentially expressed in bears and humans during disuse. This grant proposes to measure cortical bone strength, cross-sectional geometric properties (e.g., moments of inertia), and histological indices of bone formation before and after hibernation. Femurs from hunter-killed bears will be collected from voluntary donation by hunters. They will be loaded to failure in bending on a mechanical testing machine to determine the fracture strength and energy of the bones. Microscopically, the degree of porosity and level of bone formation activity will be quantified with image analysis software. The level of mineralization of the bones will be determined by quantifying the weight percentage of calcium-phosphate mineral in the bone tissue. If the bones are not weaker after hibernation than before hibernation, it will support the theory the bears have evolved biological mechanisms to prevent disuse osteoporosis. [unreadable] [unreadable] [unreadable]